The examination of the disease progression of complex diseases such as Parkinson's disease is hindered by inaccessibility of neurons and largely limited to use of postmortem samples. Primary cells from postmortem brain samples have short life-spans in vitro and the disease itself reduces in number one cell type of interest—the midbrain dopamine neuron. To date, it has been virtually impossible to use disease-affected neural tissues to screen for therapeutic agents useful for disease modification, predict disease progression and phenotype, and elucidate complex disease mechanisms. A model that replicates the fundamental features of the disease at the cellular level is needed.
Complex diseases such as Parkinson's disease, as well as many others, can involve genetic variations such as mutations and/or copy number variation (CNV) or can be idiopathic/sporadic. Induced pluripotent stem cells (iPSCs), developed from patients presenting with genetic and complex diseases, further differentiated into specific cell types, known to be affected in the natural progression of disease, will provide heretofore unavailable cellular tools for identification of disease mechanisms, therapeutic agent screening, and disease diagnosis.